The mechanisms of ion transport and cellular functions in human red blood cells are to be studied. The transport lithium which is widely used in treatment of manic depressive syndromes will be further examined to determine if the molecular mechanism for its specific exchange with sodium ions across the cell membrane is due to a simultaneous exchange of the two ions or due to a mechanism in which first lithium and then sodium is transported in a sequential fashion. We also propose to continue work on the relationship between membrane lipid composition and the function of the very rapid but specific chloride transport system of red blood cells. Thirdly, we will examine the mechanism which actively transports calcium out of cells using inside-out vesicles made from red blood cell membranes. This work seeks to determine the molecular mechanisms by which cell ion transport is performed and the regulation of this transport and thus regulation of cell ion composition.